Abstract
Within arterial bifurcations or branching points, oscillatory shear stress (OSS) induces oxidative stress mainly via the reduced nicotinamide adenine dinucleodtide phosphate (NADPH) oxidase system. It is unknown whether 17β-estradiol (E2) can regulate OSS-mediated low-density lipoprotein (LDL) modifications. Bovine aortic endothelial cells were pretreated with E2 at 5 nmol/L, followed by exposure to OSS (0 ± 3.0 dynes/cm2 s and 60 cycles/min) in a flow system. E2 decreased OSS-mediated NADPH oxidase mRNA expression, and E2-mediated {radical dot}NO production was mitigated by the NO synthase inhibitor N(G)-nitro-l-argenine methyl ester. The rates of O2 -{radical dot} production in response to OSS increased steadily as determined by superoxide-dismutase-inhibited ferricytochrome c reduction; whereas, pretreatment with E2 decreased OSS-mediated O2 -{radical dot} production (n = 4, p < 0.05). In the presence of native LDL (50 μg/mL), E2 also significantly reversed OSS-mediated LDL oxidation as determined by high-performance liquid chromatography. In the presence of O2 -{radical dot} donor, xanthine oxidase (XO), E2 further reversed XO-induced LDL lipid peroxidation (n = 3, p < 0.001). Mass spectra acquired in the m/z 400-1800 range, revealed XO-mediated LDL protein nitration involving tyrosine 2535 in the α-2 domains, whereas pretreatment with E2 reversed nitration, as supported by the changes in nitrotyrosine intensities. Thus, E2 plays an indirect antioxidative role. In addition to upregulation of endothelial {radical dot}NO synthase and downregulation of Nox4 expression, E2 influences LDL modifications via lipid peroxidation and protein nitration.
Original language | English (US) |
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Pages (from-to) | 568-578 |
Number of pages | 11 |
Journal | Free Radical Biology and Medicine |
Volume | 41 |
Issue number | 4 |
DOIs | |
State | Published - Aug 15 2006 |
Keywords
- 17β-Estradiol
- LDL lipid oxidation and nitration
- NADPH oxidase
- Nitric oxide
- Shear stress
- Superoxide anion
ASJC Scopus subject areas
- Medicine(all)
- Toxicology
- Clinical Biochemistry